Cited 283 times since 2020 (67.1 per year) source: EuropePMC Nature communications, Volume 11, Issue 1, 9 2 2020, Pages 163 Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Shah S, Henry A, Roselli C, Lin H, Sveinbjörnsson G, Fatemifar G, Hedman ÅK, Wilk JB, Morley MP, Chaffin MD, Helgadottir A, Verweij N, Dehghan A, Almgren P, Andersson C, Aragam KG, Ärnlöv J, Backman JD, Biggs ML, Bloom HL, Brandimarto J, Brown MR, Buckbinder L, Carey DJ, Chasman DI, Chen X, Chen X, Chung J, Chutkow W, Cook JP, Delgado GE, Denaxas S, Doney AS, Dörr M, Dudley SC, Dunn ME, Engström G, Esko T, Felix SB, Finan C, Ford I, Ghanbari M, Ghasemi S, Giedraitis V, Giulianini F, Gottdiener JS, Gross S, Guðbjartsson DF, Gutmann R, Haggerty CM, van der Harst P, Hyde CL, Ingelsson E, Jukema JW, Kavousi M, Khaw KT, Kleber ME, Køber L, Koekemoer A, Langenberg C, Lind L, Lindgren CM, London B, Lotta LA, Lovering RC, Luan J, Magnusson P, Mahajan A, Margulies KB, März W, Melander O, Mordi IR, Morgan T, Morris AD, Morris AP, Morrison AC, Nagle MW, Nelson CP, Niessner A, Niiranen T, O'Donoghue ML, Owens AT, Palmer CNA, Parry HM, Perola M, Portilla-Fernandez E, Psaty BM, Regeneron Genetics Center, Rice KM, Ridker PM

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

Nat Commun. 2020 1;11(1):163